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离子通道对……翅膀发育的贡献

Ion Channel Contributions to Wing Development in .

作者信息

George Laura Faith, Pradhan Sarala Joshi, Mitchell Danae, Josey Megan, Casey Justin, Belus Matthew T, Fedder Karlie N, Dahal Giri Raj, Bates Emily Anne

机构信息

Department of Pediatrics, University of Colorado School of Medicine; Aurora, CO, 80045.

Department of Pediatrics, University of Colorado School of Medicine; Aurora, CO, 80045

出版信息

G3 (Bethesda). 2019 Apr 9;9(4):999-1008. doi: 10.1534/g3.119.400028.

Abstract

During morphogenesis, cells communicate with each other to shape tissues and organs. Several lines of recent evidence indicate that ion channels play a key role in cellular signaling and tissue morphogenesis. However, little is known about the scope of specific ion-channel types that impinge upon developmental pathways. The wing is an excellent model in which to address this problem as wing vein patterning is acutely sensitive to changes in developmental pathways. We conducted a screen of 180 ion channels expressed in the wing using loss-of-function mutant and RNAi lines. Here we identify 44 candidates that significantly impacted development of the wing. Calcium, sodium, potassium, chloride, and ligand-gated cation channels were all identified in our screen, suggesting that a wide variety of ion channel types are important for development. Ion channels belonging to the pickpocket family, the ionotropic receptor family, and the bestrophin family were highly represented among the candidates of our screen. Seven new ion channels with human orthologs that have been implicated in human channelopathies were also identified. Many of the human orthologs of the channels identified in our screen are targets of common general anesthetics, anti-seizure and anti-hypertension drugs, as well as alcohol and nicotine. Our results confirm the importance of ion channels in morphogenesis and identify a number of ion channels that will provide the basis for future studies to understand the role of ion channels in development.

摘要

在形态发生过程中,细胞相互交流以塑造组织和器官。最近的几条证据表明,离子通道在细胞信号传导和组织形态发生中起关键作用。然而,对于影响发育途径的特定离子通道类型的范围知之甚少。翅膀是解决这个问题的一个极好模型,因为翅脉模式对发育途径的变化非常敏感。我们使用功能丧失突变体和RNAi品系对翅膀中表达的180种离子通道进行了筛选。在这里,我们鉴定出44个对翅膀发育有显著影响的候选基因。我们的筛选中鉴定出了钙、钠、钾、氯和配体门控阳离子通道,这表明多种离子通道类型对发育很重要。属于扒手家族、离子型受体家族和最佳rophin家族的离子通道在我们筛选的候选基因中高度富集。还鉴定出了七个与人类通道病有关的具有人类同源物的新离子通道。我们筛选中鉴定出的通道的许多人类同源物是常见全身麻醉剂、抗癫痫和抗高血压药物以及酒精和尼古丁的靶点。我们的结果证实了离子通道在形态发生中的重要性,并鉴定出了一些离子通道,这些通道将为未来研究理解离子通道在发育中的作用提供基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef7c/6469425/e1e056349046/999f1.jpg

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